1. Technical Field
The present invention relates generally to the field of transesterification reactions for regulating copolymer physico-mechanical and biological properties and more specifically to the use of lipase-catalyzed selective transesterification reactions to construct novel polymers.
2. Prior Art
Chemical methods that result in the copolymerization of two or more monomers are a key strategy for the xe2x80x98tailoringxe2x80x99 of polymeric materials. Unfortunately, in many cases, important copolymer compositions and repeat unit sequences that may offer key property benefits are not attainable by using existing methods. Also, chemical methods to catalyze polymer-polymer transesterification reactions have met with limited success due to the need for high-temperature reactions that lead to undesirable chain decomposition including molecular weight decrease. However, such transesterification reactions are extremely valuable for regulating copolymer physico-mechanical and biological properties.
Transesterification reactions between preformed polymers, a monomer-polymer pair, or two monomers, are of importance in industry to rapidly xe2x80x98tunexe2x80x99 physico-mechanical and biological properties. In addition, many commercially important blends contain polyesters as one or more components that may undergo transesterification reactions during melt processing. In the pursuit of efficient transesterification reactions, it often is necessary to use high temperatures and catalysts that leave toxic residues in products. Furthermore, these chemical routes do not provide selectivity over the site at which chains are cleaved during exchange reactions. Moreover, these reactions often lead to non-desired side reactions that decrease product molecular weight and/or produce colored substances.
Therefore, it is evident that there is a need for transesterification reactions that can proceed at lower temperatures, with catalysts that do not leave toxic residues, do not lead to non-desired side reactions, and provide selectivity over the site at which chains are cleaved during exchange reactions. It is to this need that the present invention is directed.
The use of lipases in monophasic organic media has proved useful to facilitate mild selective transesterification reactions of low molecular weight substances. In the present invention, lipase-catalyzed selective transesterification reactions are used to construct novel polymers. An important advantage of the present invention is the ability to regulate the copolymer repeat unit sequence distribution. In addition, the lipase-catalyzed transesterification reactions of the present invention take place with chain-length specificity. In other words, activation of chains for exchange reactions with other chains or monomers can occur preferentially at certain locations along the chain.
The new methods disclosed herein have led to important new polymer compositions where repeat units are linked by ester, carbonate, amide, ether or various combinations of these bonds. Examples of uses for the polymers prepared by the present invention are plastics, adhesives, coatings, biodegradable plastics, bioresorbable implant materials, to aid wound healing of burn patients, as scaffolds for cell growth and in drug release formulations. Methods are disclosed by which lipases catalyze the formation of copolymers by reactions between two or more preformed polyesters, polyester and a monomer (such as lactone or cyclic carbonate), a polycarbonate and a monomer, and reactions between two or more monomers.
The novel method to regulate copolymer structure using lipase catalyzed transesterification reactions disclosed herein comprises the general steps of selecting a first reactant from the group consisting of polymers and monomers, selecting a second reactant from the group consisting of polymers and monomers, and combining the first reactant, the second reactant, and a lipase in a reaction vessel and allowing the ensuing transesterification reaction to proceed resulting in a desired polymer. Preferably a solvent also is present in the reaction vessel. The lipase preferably is an immobilized lipase maintained at approximately 70xc2x0 C., and the reaction is allowed to proceed for between 1 min and 24 hr depending on the product desired.
The present invention discloses the lipase-catalyzed synthesis of copolymers having mixed linkages such as ester/ether, ester/carbonate and ether/carbonate. Lipase-catalyzed transesterification reactions may be used to form copolymers that are random, diblock, multiblock or some other arrangement of repeat units along a copolymer chain. For example, lipases may be used to catalyze transesterification reactions between combinations of structurally different lactones, lactones with polyesters, lactones with copoly(ester/amides) and polyesters with polyesters. Also, lipases may be used to catalyze exchange reactions between polyesters and polycarbonates to form chains having mixed linkages such as, for example, ester/carbonate. Other lipase catalyzed exchange reactions may be between polyesters and polyethers to form copoly(ester/ethers) or polycarbonates and polyethers to form copoly(carbonate/ethers).
Reaction parameters such as the substrates, temperature, time, solvent (or the lack of one), lipase, and method of lipase activation can all be used to engineer the desired repeat unit sequence of copolymers. Also, the molecular weight of polymers used for exchange reactions is a critical parameter. For example, poly(xcex5-caprolactone-co-xcfx89-pentadecalactone), P(CL-co-PDL), was synthesized by variation in the substrates used to form the copolymer. The example copolymerizations are performed by lipase-catalyzed transesterification reactions between the following substrate pairs: xcex5-CL/PDL, PCL/PDL, poly(xcfx89-pentadecalactone) (PPDL)/xcex5-CL, PPDL/PCL and poly(trimethylene carbonate-co-pentadecalactone), P(TMC-co-PDL). The preferred catalyst is Novozym-435 and the preferred solvent is toluene. All of the above reactions result in the formation of copolymers that differ substantially in their microstructure.
The invention discloses the use of lipase-catalyzed transesterification reactions between different preformed polymers as well as between polymers and monomers. This route to copolymers provides important elements of control over the copolymer repeat unit sequence. Furthermore, enzyme-catalysis provides a route that can have other benefits such as: i) decreased reaction temperatures relative to conventional chemical catalysts; ii) rapid ester interchange kinetics; and iii) selectivity over chain compositions that undergo interchange. The selectivity of preferred sites for ester interchange reactions can result from differences in the side group or main chain structural elements including variations in stereochemical composition. Thus, lipase-catalysis offers a new and powerful route to engineer copolymer structure during transesterification reactions.
It is an object of the present invention to provide a transesterification reaction to regulate copolymer structure.
It is another object of the present invention to provide a transesterification reaction to regulate copolymer structure that is lipase catalyzed and does not leave toxic residues in product polymers.
It is another object of the present invention to provide a transesterification is reaction to regulate copolymer structure that proceeds at lower temperatures thus reducing undesirable chain decomposition.
It is another object of the present invention to provide a transesterification reaction to regulate copolymer structure that does not lead to non-desired side reactions that decrease product molecular weight.
It is another object of the present invention to provide a transesterification reaction to regulate copolymer structure that does not lead to non-desired side reactions that produce colored substances.
It is another object of the present invention to provide a transesterification reaction to regulate copolymer structure that provides selectivity over the site at which chains are cleaved during exchange reactions.
These objects, and other objects, features and advantages of the present invention will become more apparent to those of ordinary skill in the art when the following detailed description of the preferred embodiments is read in conjunction with the appended figures.